Desire to be youthful to the end of time is a humans' common and universal desire, however, all humankind have experienced for long to have appeared wrinkles, fine wrinkles, blemishes, or saggings in the skin as they become older. Ageing also causes skin ageing, and the appearance of apparent changes such as wrinkles, fine wrinkles, blemishes, or saggings in the skin has been recognized to be so called natural providence as an unavoidable thing.
Recently, however, causatives or mechanisms of apparent changes such as wrinkles, blemishes, or saggings in the skin with ageing are gradually being revealed as the progress of researches on the structure and the metabolic mechanism of human skin. As well known, the skin is constructed by the outer thin epidermis (epithelium tissue) and the lower layered thick dermis (connective tissue); and the epidermis, as the outermost layer, protects living bodies from the outside world and prevents the leakage of internal moisture and nutrients to the outside of the bodies. While, the dermis is a connective tissue having the structure, where fibroblasts, collagens, elastins, proteoglycans and the like mainly spread complexly and three-dimensionally, which has roles for imparting strength, extensibility, and elasticity to the skin; however, the moisture-retaining ability of the cuticle in the skin surface will be lost as the decrease of sebum and moisture contents in the skin with ageing and it may become to easily induce fine wrinkles and rough skin due to dryness of the skin or the like.
Human epidermis, which is constructed by “keratinous layer” (stratum corneum), “granular layer”, “stratum spinosum”, and “stratum germinativum” located in this order from the outersurface, is finally cast off as a result of keratinocyte generated in the stratum germinativum, and sequentially moved to the outer surface. In particular, keratinocyte is proliferated in the stratum germinativum located in the innermost of the epidermis, differentiated, moved upward, finally turned into the keratinous layer located in the outermost of the keratinous layer (stratum corneum), and then desquamated as scurf. Such serial process of proliferation, movement, differentiation, and desquamation is called turnover, where the skin homeostasis is retained by newly rebirthing keratinocyte at a constant cycle that may induce wrinkles, saggings, and rough skin by delaying the turnover rate of the skin with ageing. Though the turnover rate of the skin varies depending on the sites of the body, it is said that healthy teenagers have a turnover rate of about 20 days; twenties, about 28 days; thirties, about 40 days; forties, about 55 days as roughly two times of that of twenties; and fifties, about 75 days. By the way, even if the turnover rate of the skin becomes fast or slow, it should not be preferable, while the normal skin turnover rate is recognized to be 28 days as that of twenties. The reason is that, when the turnover rate is fast, the level of melanin pigment, produced by melanocytes, for absorbing ultraviolet rays in the skin will increase; and this accelerates cosmetically-unfavorable melanin pigmentation by ultraviolet rays.
It is said that, as a recent finding, in vivo glycation in the skin (simply called “glycation”, hereinafter) relates to the delaying of skin turnover rate and associates with skin ageing. Glycation may be also called Maillard reaction (or browning reaction) and meant as a process ranging from the binding of reducing saccharides such as glucose and fructose with the epidermis (collagen) or the keratinous layer (keratin) to the formation of substances called advanced glycation end products, i.e. AGEs. It is recognized that AGEs deposit on skin tissues and bind to a receptor for AGEs called RAGE; induce an inflammatory change in the skin or other tissues; form disorganized linkages in collagen intra- and inter-molecularly during the formation of AGEs to induce physical or physiological changes (deteriorations) on collagen; and cause skin ageing such as wrinkles, rough skin, saggings, or the reduction of skin firmness. It is also said that collagen, wherein disorganized linkages are formed intra- or inter-molecularly through glycation, would lose elasticity and become to be hardly decomposed by in vivo proteases, resulting in a delaying of skin turnover rate (see Non Patent Literature 1).
As described above, since the delaying of skin turnover rate with ageing is said to induce wrinkles, saggings, or rough skin, if any means for making up for a delayed turnover rate with ageing would be avairable, even though it is really hard to catch up the delayed turnover rate of the skin of a so called pre-ageing generation, including those in the around 30- to 50-year-old age group who start worrying about the above-identified skin conditions, to the level of the twenties as the normal skin turnover rate, it would possibly effectively improve such wrinkles, saggings, or rough skin. From this aspect, turnover rate may possibly be improved by either accelerating the turnover rate through the promotion of at least one step among sequential series of proliferation, migration, differentiation, and desquamation; or inhibiting glycation recognized as to induce the delaying of turnover rate; however, any actual means for solving it has not yet been provided.
When fibroblasts and hyaluronic acid in the dermis may be reduced with ageing or the breakage of collagen and the deterioration of elastin may be induced with ageing, wrinkles are allegedly formed or the elasticity of the skin are said to be lowered to cause dull or rough skin. There is also a finding that a non-smooth egestion of melanin excreted from melanocytes to epidermal cells may be causative for pigmentation (blemishes) and dullness of the skin.
Based on these research results and findings, at present, there can be seen proposals (see, for example, Patent Literatures 1 to 7) so called external dermal agents for anti-ageing that theoretically prevent or improve the apparent changes such as wrinkles, fine wrinkles, blemishes, saggings in the skin, or the like in the skin with ageing, in terms of scientific point of view, whereby humans are getting nearer to the realization of the desire to keep youthfulness to the end of time step by step. Currently-proposed external dermal agents for anti-ageing, however, have only pursued and realized quite partial possibilities from among many possibilities. Accordingly, there is still desired a providing of a novel external dermal agent for anti-ageing from different angles, including distinctly different mechanisms of exerting anti-ageing effects from currently-proposed external dermal agents for anti-ageing, which have been merely realized as a result of pursuing only a part of various possibilities, conveniences, and production feasibilities.